DESCRIPTION: The principal working hypothesis proposed in this application is that developmental exposure to organochlorines can disrupt brain development by interfering with thyroid hormone function in the fetal brain. The three specific aims are: (1) to determine whether a specific PCB mixture alters the expression of thyroid hormone receptors (TRs), the retinoic acid receptors (RAR/RXRs) which are known to interact with TRs, or the aryl hydrocarbon receptor (AhR) during development of the inner ear, (2) to determine whether developmental exposure to a specific PCB mixture produces morphological abnormalities consistent with those induced by hypothyroidism, and (3), to determine whether developmental exposure to PCBs disrupts the known, orderly sequence of gene expression in the developing cochlea.